Differential genome-wide profiling of alternative polyadenylation sites in nasopharyngeal carcinoma by high-throughput sequencing.
Differential genome-wide profiling of alternative polyadenylation sites in nasopharyngeal carcinoma by high-throughput sequencing.
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通过高通量测序对鼻咽癌中替代多聚腺苷酸化位点进行全基因组差异分析。
DOI：
10.1186/s12929-018-0477-6
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发表时间：
2018-10-23
影响因子：
11
通讯作者：
Tang LL
中科院分区：
文献类型：
--
作者：
Xu YF;Li YQ;Liu N;He QM;Tang XR;Wen X;Yang XJ;Sun Y;Ma J;Tang LL
选择性多聚腺苷酸化(APA)是转录后基因表达调控中的一种普遍现象，可产生具有3‘非翻译区(3’UTRs)的mRNAs。APA与包括癌症在内的各种疾病的发病机制有关。然而，APA在鼻咽癌(NPC)发生发展中的潜在作用在很大程度上仍不清楚。采用基于第二代测序技术的APA位点测序策略，从6例鼻咽癌组织和6例正常鼻咽上皮组织标本中寻找APA位点的全球模式，并利用串联3‘UTRs进行基因鉴定。测序结果随后在16个鼻咽癌和16个NNET样本的更大队列中使用定量RT-PCR进行了验证。测序数据表明，串联APA位点在鼻咽癌中普遍存在，并发现了大量具有APA开关事件的基因。总之，我们鉴定了195个在鼻咽癌和Nnet之间串联3‘非编码区长度有显著差异的基因；其中119个基因切换到远端的PolyA位点，76个基因切换到近端的PolyA位点。一些基因本体论(GO)术语被丰富在APA位点转换的基因列表中，包括细胞迁移调节、大分子分解代谢过程、蛋白质分解过程、蛋白分解、小结合蛋白连接酶活性和泛素蛋白连接酶活性。APA位点转换事件在鼻咽癌中普遍存在。APA介导的基因表达调控可能在鼻咽癌的发生发展中起重要作用，更详细的针对APA开关事件基因的研究可能有助于开发新的鼻咽癌治疗策略。本文的在线版本(10.1186/s12929-0180477-6)包含补充材料，可供授权用户使用。
Alternative polyadenylation (APA) is a widespread phenomenon in the posttranscriptional regulation of gene expression that generates mRNAs with alternative 3′-untranslated regions (3’UTRs). APA contributes to the pathogenesis of various diseases, including cancer. However, the potential role of APA in the development of nasopharyngeal carcinoma (NPC) remains largely unknown. A strategy of sequencing APA sites (SAPAS) based on second-generation sequencing technology was carried out to explore the global patterns of APA sites and identify genes with tandem 3’UTRs in samples from 6 NPC and 6 normal nasopharyngeal epithelial tissue (NNET). Sequencing results were then validated using quantitative RT-PCR in a larger cohort of 16 NPC and 16 NNET samples. The sequencing data showed that the use of tandem APA sites was prevalent in NPC, and numerous genes with APA-switching events were discovered. In total, we identified 195 genes with significant differences in the tandem 3’UTR length between NPC and NNET; including 119 genes switching to distal poly (A) sites and 76 genes switching to proximal poly (A) sites. Several gene ontology (GO) terms were enriched in the list of genes with switched APA sites, including regulation of cell migration, macromolecule catabolic process, protein catabolic process, proteolysis, small conjugating protein ligase activity, and ubiquitin-protein ligase activity. APA site-switching events are prevalent in NPC. APA-mediated regulation of gene expression may play an important role in the development of NPC, and more detailed studies targeting genes with APA-switching events may contribute to the development of novel future therapeutic strategies for NPC. The online version of this article (10.1186/s12929-018-0477-6) contains supplementary material, which is available to authorized users.
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影响因子：
64.5
作者：
Cooper TA;Wan L;Dreyfuss G
通讯作者：
Dreyfuss G
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作者：
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Feng, BJ;Huang, W;Zeng, YX
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Agami, Reuven